tbuckley/cabot-search huggingface dataset:
P85 Switching from adalimumab originator to biosimilar: a 3-year retrospective cohort analysis
Authors: Lisa Killion, Ali Alsharqi, Brian Kirby
Journal: British Journal of Dermatology (2023)

Abstract Biological drugs have revolutionized the treatment of immune-mediated inflammatory diseases. Clinical experience and evidence suggest that biosimilars can be used as safely and effectively as their originator. However, patients’ perceptions of biosimilars are that they are inferior to the originator. Currently, few studies have assessed the tolerability and efficacy of switching from the adalimumab originator to a biosimilar in patients with well-controlled moderate-to-severe psoriasis. Our objective was to describe the clinical experience of switching patients from the adalimumab originator to a biosimilar and that of switching back to the originator for those intolerant to biosimilars. A single-centre, retrospective cohort study was conducted to identify patients with moderate-to-severe psoriasis who had switched from the adalimumab originator (Humira®) to a biosimilar (Amgevita® or Imraldi®) from 2018 to 2022. Patient data were obtained from a combination of patient records and databases, including the British Association of Dermatologists Biologics and Immunomodulators Register (BADBIR) and the National High Tech Prescribing Hub. Patients were excluded from the study if their treatment duration on an adalimumab biosimilar was &amp;lt; 16 weeks or if they were being treated for an indication other than psoriasis. From 2018 to 2022, 100 patients who switched from the adalimumab originator to a biosimilar were identified. At week 16, 81 patients (81%) maintained their initial switch from the adalimumab originator to biosimilar. Nineteen (19%) patients who were switched to an adalimumab biosimilar were switched back to the originator secondary to adverse events. Maintenance or improvement in baseline Psoriasis Area and Severity Index (PASI) and Dermatology Life Quality Index (DLQI) was observed in 91% and 90%, respectively, in patients who remained on a biosimilar. For those intolerant to biosimilars, maintenance or improvement in baseline PASI and DLQI was still observed although in fewer patients: 63% and 47%, respectively. Our study demonstrates that drug efficacy was recaptured and adverse events were ameliorated for all patients switched from an adalimumab biosimilar back to the originator. For patients who did not tolerate biosimilar switch, reasons for switching back to the originator mirrored those reported in the literature. All patients who switched back to the originator from a biosimilar recovered from loss of efficiency and the adverse events they had reported. Physicians should be confident in switching patients with well-controlled psoriasis to adalimumab biosimilars. For the small proportion of patients who experienced loss of efficacy or adverse events, all were recaptured by either switching to an alternative adalimumab biosimilar or switching back to the adalimumab originator.
P107 Clinical priorities when treating psoriasis: insights from a real-world data study of tildrakizumab
Authors: Gabrielle Becher, Karen Stephen, Alison McInnes, Adrian Heald, Paul Riley, Mark Davies, Murad Ali, Ismail Kasujee
Journal: British Journal of Dermatology (2023)

Abstract Achieving clear skin when treating psoriasis is the clinical priority for some clinicians, but it may not be the priority for all patients; wellbeing may be more important. To gain insights into the relative importance of clear skin for wellbeing, we retrospectively reviewed real-world data from four specialist dermatology departments in England and Scotland. We assessed the evolution in absolute Psoriasis Area and Severity Index (PASI) and Dermatology Life Quality Index (DLQI) scores in 122 adults treated with tildrakizumab for plaque psoriasis, to determine whether a reduction in PASI scores to &amp;lt; 3 or &amp;lt; 1 was needed to achieve a DLQI of 1 or 0. Mean age was 49 years (range 17–82). Median time since diagnosis was 18 years (range 4–67). Median time on treatment with tildrakizumab was 9 months (range 1–21). At baseline, the median PASI score was 12 (range 0–40) and median DLQI was 20 (range 0–30). The proportion of patients with PASI &amp;lt; 3 increased from 6% at baseline to 60% at final visit, and with PASI &amp;lt; 1 from 3% to 48%. The proportion of patients with PASI &amp;lt; 1 was greater for patients having &amp;gt; 52 weeks of data (61%) than for patients having &amp;gt; 28 weeks of data (52%). The median DLQI score at baseline was 20 (range 0–30) and that at final visit was 1 (range 0–22). The proportion of patients with a DLQI of 0 or 1 increased from 4% at baseline to 54% at final visit. The proportion of patients with a DLQI of 0 or 1 was no different for patients having &amp;gt; 52 weeks of data (52%) than for patients having &amp;gt; 28 weeks of data (56%). An improvement in the PASI score to &amp;lt; 1 or &amp;lt; 3 was accompanied by a reduction in DLQI to 1 or 0, but it was not a requirement. Tildrakizumab demonstrated substantial improvement in psoriasis signs and in patient quality of life comparable with other interleukin (IL)-23 inhibitors in UK clinical practice. The PASI score decreased and was maintained in line with the thinking that IL-23p19 antagonists such as tildrakizumab have good survival. An improvement in the PASI score to &amp;lt; 1 or &amp;lt; 3 may not be necessary for a patient to feel that their life is unaffected by their psoriasis. It may be prudent for clinicians to prioritize patient wellness and durability of treatment rather than aim for clear skin in every patient. Funding sources: Almirall.
P62 The environmental impact of skin cancer surgery
Authors: Sarah Fleming, Ciara Drumm, Ciara O’Donnell, Sorcha Lynch, Aoife Lally, Blaithin Moriarty
Journal: British Journal of Dermatology (2023)

Abstract The climate crisis has been described as the greatest global health threat by the World Health Organization. In 2019, healthcare-related emissions accounted for 25 mega-tonnes CO2 equivalent (CO2e), 10% of which was related to staff and patient travel. In the UK, 3.5% of road use is related to the National Health Service. The healthcare sector must recognize its role in contributing to carbon emissions and commit to taking decisive action to reduce these. Health-care generates a significant proportion of global emissions; a 2021 report by the Lancet estimated that the healthcare sector contributes to 4.9% of greenhouse gas emissions. As the impact of these numbers is coming to the fore, sustainable health care is becoming a necessity. This study aimed to determine the reduction in CO2e from same-day surgery for patients at skin cancer clinics. CO2e from travel by patients undergoing surgical procedures in a 6-month period (July–December 2020) were calculated. Data collected included age, diagnosis, site of lesion and total number of visits. The distance from the patient’s address was calculated using Google Maps. Total CO2e was calculated using an online calculator recommended by the Environmental Protection Agency of Ireland. A total of 299 patients had 319 procedures between July and December 2020. The median (SD) patient age was 68 (18.5) years (range 16–97). The total distance travelled by patients was 26 069 km, with a mean of 86 km travelled per patient (range 1.2–789). This generated 4.47 tonnes of CO2e emissions (range 0.0–0.6 tonnes). In total, 225/299 patients (75.2%) had surgery on the same day as their clinic appointment. They travelled a total average distance of 72 km (range 1.2–464), with a median of one hospital visit (range 1–2). Seventy-four of 299 patients (24.7%) had alternative day surgery, travelling an average distance of 129 km (range 8.4–789 km), with a median of two hospital visits (range 1–5). The mean CO2e for patients attending for same-day procedures was 0.017 tonnes (range 0–0.6) vs. 0.024 tonnes (range 0–0.16) for alternate-day procedures, a reduction of 0.007 tonnes (30%) per patient (P = 0.3). The introduction of same-day surgery for patients resulted in a 2.93-tonne (55%) reduction in CO2e, the equivalent to driving from the north to the south of Ireland 13 times (8000 km). We have demonstrated a reproducible innovative approach to the reduction of the carbon footprint generated by the management of skin cancer. With ever-increasing demands on the healthcare system, it is vital that we use innovative ways to reduce the carbon footprint generated. The actions of the healthcare sector now will affect the health and wellbeing of generations to come.
P84 Efficacy and safety of lebrikizumab at 16 weeks: pooled analyses from ADvocate1 and ADvocate2 phase III trials in patients with moderate-to-severe atopic dermatitis
Authors: Richard B Warren, Jonathan I Silverberg, Emma Guttman-Yassky, Diamant Thaçi, Alan Irvine, Linda Stein Gold, Andrew Blauvelt, Eric L Simpson, Chia-Yu Chu, Zhuqing T Liu, Renata Gontijo Lima, Sreekumar Pillai, Esther Garcia Gil, Julien Seneschal
Journal: British Journal of Dermatology (2023)

Abstract Lebrikizumab (LEB) is a high-affinity monoclonal antibody targeting interleukin (IL)-13, preventing IL-13 signalling via the IL-4Rα/IL-13Rα1 receptor complex. Here, we report 16-week efficacy and safety outcomes of LEB monotherapy in patients with moderate-to-severe atopic dermatitis from two 52-week, randomized, double-blinded, placebo-controlled phase III trials, ADvocate1 (NCT04146363) and ADvocate2 (NCT04178967). Eligible adults and adolescents (aged 12–17 years, weighing ≥ 40 kg) from ADvocate1 and ADvocate2 were randomized (2 : 1) to subcutaneous LEB 250 mg (500 mg loading dose at baseline and week 2) or placebo every 2 weeks (Q2W). Efficacy analyses included proportions of patients achieving Investigator’s Global Assessment (IGA) 0/1 and Eczema Area and Severity Index (EASI)-75 (coprimary endpoints), EASI-90, and pruritus numeric rating scale (NRS) ≥ 4-point improvement from baseline to week 16. This was a pooled analysis of ADvocate1 and ADvocate2, where IGA 0/1 and EASI-75 and EASI-90 were analysed in 564 and 287 patients (LEB 250 mg and placebo), respectively, and pruritus NRS in 516 and 264 patients, respectively. Cochran–Mantel–Haenszel with Markov chain Monte Carlo multiple imputation was performed. Patients treated with LEB 250 mg and placebo for 16 weeks achieved, respectively, IGA 0/1 response rates of 38.1% (n = 215) and 11.7% (n = 34; P &amp;lt; 0.001); EASI-75 responses of 55.4% (n = 313) and 17.2% (n = 49; P &amp;lt; 0.001); EASI-90 responses of 34.5% (n = 195) and 9.2% (n = 26) (P &amp;lt; 0.001); and pruritus NRS ≥ 4-point improvement responses of 42.9% (n = 221) and 12.2% (n = 32; P &amp;lt; 0.001). The percentage of patients reporting one or more treatment emergent adverse event(s) was lower in the LEB group (49.6%) than in the placebo group (59.0%; P = 0.009). These data suggest that LEB 250 mg Q2W for 16 weeks is an efficacious and safe treatment option for adult and adolescent patients with moderate-to-severe atopic dermatitis. Funding sourcesThis study was funded by Dermira, a wholly owned subsidiary of Eli Lilly and Company. Almirall has licensed the rights to develop and commercialize lebrikizumab for the treatment of dermatology indications, including atopic dermatitis, in Europe. Lilly has exclusive rights for development and commercialization of lebrikizumab in the United States and the rest of world outside Europe.
P38 Integrating proteomics and genomics to investigate the mechanisms of paradoxical eczema developing in patients with psoriasis treated with biologics: a UK multicentre, longitudinal, cohort study
Authors: Ali Al-Janabi, Paul Martin, Adnan Khan, Amy Foulkes, Catherine Smith, Christopher Griffiths, Andrew Morris, Steve Eyre, Richard Warren
Journal: British Journal of Dermatology (2023)

Abstract Few studies have explored the immunology and genetic risk of paradoxical eczema occurring in patients with psoriasis treated with biologics. This study aims to describe the systemic inflammatory signature of paradoxical eczema using proteomics and explore whether it is genetically mediated. Participants were adults treated with biologics for plaque psoriasis, who were corecruited to the British Association of Dermatologists Biologics and Immunomodulators Register (BADBIR) and Biomarkers of Systemic Treatment Outcomes in Psoriasis (BSTOP) studies. To identify differentially expressed proteins and enriched gene sets, we used the Olink Target 96 Inflammation panel on 256 serum samples from BSTOP for 71 cases with paradoxical eczema and 75 controls. Paradoxical eczema was defined as eczema, atopic eczema or atopic dermatitis occurring during biologic exposure. Case samples across three time points [T1: prebiologic (n = 42); T2, postbiologic (n = 45); T3, postparadoxical eczema (n = 41)] were matched 1 : 1 with control samples. Case samples at T2 and T3 were taken during exposure to the same biologic that caused paradoxical eczema. Genes contributing to proteomic signatures were selected, and single-nucleotide polymorphisms (SNPs) that were nonsynonymous or associated with significant expression quantitative trait loci were used to create polygenic risk scores (PRS) in a genotyped cohort of 88 paradoxical eczema cases and 3124 psoriasis controls. Signal transducing adapter molecule 1-binding protein expression was lower in cases at T1 than in controls (log-fold change −0.44, adjusted P = 0.022); no other proteins achieved statistical significance at equivalent time points. Eleven gene sets, including cytokine and chemokine pathways, were enriched in cases at T2 and 10 at T3. Of the 39 proteins contributing to enriched gene sets, 21 are elevated in the sera of patients with atopic dermatitis. A PRS including 38 SNPs linked to enriched gene sets was associated with paradoxical eczema (adjusted P = 0.046). We subdivided the SNPs into those linked to specific gene sets, such as chemokine, cytokine and interleukin (IL)-10 signalling, to generate 10 partitioned PRS. Seven were associated with paradoxical eczema (adjusted P &amp;lt; 0.05). These SNPs do not map to known atopic loci. The paradoxical eczema systemic inflammatory proteome trends toward atopic dermatitis at a gene set level and is detectable before the onset of the phenotype. This signature may be mediated genetically by SNPs associated with these gene sets. Further studies are needed to explore the role of specific pathways (such as IL-10 signalling) in paradoxical eczema and define the inflammatory profile in the skin.
PA14 Aquagenic palmar wrinkling in a 15-year-old swimmer
Authors: Emma Porter, Cathal O’Connor, Lesley-Ann Murphy
Journal: British Journal of Dermatology (2023)

Abstract A 15-year-old girl presented with a 1-year history of recurrent palmar wrinkling on contact with water. This was associated with a burning sensation within minutes of water exposure and progressive persistent thickening of the palmar skin. She was otherwise well, with no family history of note, including cystic fibrosis (CF). She had no regular medication or newly introduced medications before the onset of wrinkling. Moderate improvement in hyperkeratosis was seen with twice-daily use of urea 10% and salicylic acid 10% creams; however, the discomfort experienced in water was negatively affecting her ability to continue competitive swimming. On examination, there was palmar hyperlinearity with focal hyperkeratosis over the thenar and hypothenar eminences. Immersion of the hands in lukewarm water resulted in wrinkling within 2 min and peaking at 3 min, at which point the patient reported a burning sensation. Wrinkling resolved within 30 min of drying her hands. Baseline laboratory investigations were normal. Biopsy of the palm in the wrinkled state showed subtle prominence and dilation of sweat gland ducts. A diagnosis of aquagenic syringeal keratoderma (ASK) was made. At the 3- and 6-month reviews, the patient reported spontaneous resolution of wrinkling on contact with water, which was confirmed clinically. Residual hyperkeratosis had similarly resolved, although subtle palmar hyperlinearity persisted. She was able to resume competitive swimming activities without symptoms. The ASK is a rare condition, classically affecting the palms of young women, in which palmar wrinkling occurs within minutes of immersion in water. It may be asymptomatic or associated with stinging, burning or paraesthesia. Palmar wrinkling typically resolves after drying of the hands without persisting signs. The mechanism for this phenomenon is unclear, with theories including acquired abnormalities in eccrine glands, an underlying primary keratoderma, or potential induction by cyclooxygenase. Aquagenic palmar wrinkling is also recognized in association with CF, both in individuals with the disease and carriers, with more rapid onset of wrinkling in the former. In this case, there was no suggestion of personal or family histories of CF, and hyperkeratosis persisted for months at a time until liberal regular use of keratolytic topical agents was introduced. Hereditary papulotranslucent acrokeratoderma, a differential diagnosis in this case, was considered; however, in this condition once papules and wrinkling appear, they typically remain and are further exacerbated by water exposure. For this patient, a diagnosis of atypical ASK was favoured due to the persisting sequelae, with probable mild atopic dermatitis reflected by palmar hyperlinearity. This case serves to highlight this rare dermatological phenomenon and its impact on a teenage swimmer.
PA18 Pityriasis rotunda associated with glucose-6-phosphate deficiency in an adolescent boy
Authors: Samuel Ashcroft, Senthil Murali
Journal: British Journal of Dermatology (2023)

Abstract Pityriasis rotunda is an uncommon disorder related to abnormal keratinization, which is characterized clinically by well-defined, scaly, round hypo- or hyperpigmented plaques present over the buttocks, thighs, trunk and lower limbs. It is thought to be a form of acquired ichthyosis. Two types of pityriasis rotunda are often described: type 1, which typically presents in Black and Asian patients &amp;gt; 60 years of age, and is often associated with systemic disease or malignancy; and type 2, which typically presents in patients &amp;lt; 40 years and without associated systemic disease, and may have a familial component. Pityriasis rotunda is particularly rare in children, although case reports have been published in the literature. We present an unusual case of pityriasis rotunda presenting in a 13-year-old boy of Ghanaian descent, with no significant family history. Examination demonstrated typical discrete, hyperpigmented, oval-shaped plaques appearing on the lower limbs and thighs. Biopsy demonstrated typical orthokeratosis, an attenuated granular layer and hyperpigmentation of basal keratinocytes. He was subsequently diagnosed with glucose-6-phosphate dehydrogenase deficiency, which is reported to be associated with pityriasis rotunda. This represents a rare case of pityriasis rotunda presenting in childhood, and may support an association with glucose-6-phosphate dehydrogenase deficiency.
P61 Cutaneous malignant melanoma diagnosed on nonvisible body sites and the importance of total body examination: a retrospective cohort study
Authors: Anna Wolinska, Stephanie Bowe, Gregg Murray, Sinead Collins, Cliona Feighery, Muireann Roche, Aizuri Murad
Journal: British Journal of Dermatology (2023)

Abstract The incidence of cutaneous malignant melanoma (MM) is increasing worldwide. Regular self-skin examination can assist in the early detection of MM. However, identifying new or changing lesions on nonvisible body sites (NVBS) can be difficult. Research investigating MM on NVBS is limited. The aim of this study was to compare the features of MM on NVBS with visible body sites (VBS) to add data to this patient cohort. We performed a retrospective chart review to identify patients diagnosed with MM in our institution from 2019 to 2021. Clinicopathological features were extracted and analysed. NVBS was defined as areas including the posterior scalp, ears and neck, posterior shoulder, back, buttocks, posterior thigh and plantar aspect of the feet. Statistical analysis was performed using SPSS (IBM). A total of 162 patients were included in this study; 45.1% (n = 73) were male. Patients with MM on NVBS were statistically significantly younger (median age 59 years) compared with patients with MM on VBS (median age 66.5 years; P &amp;lt; 0.05). Thirty-seven per cent (n = 60) of lesions were found on NVBS. Twenty-eight per cent (n = 17) of MMs on NVBS were identified incidentally on total body examination (TBE) in the clinic by a dermatologist. There was a statistically significantly higher number of patients with melanoma in situ on VBS (n = 44; 27.1%) compared with NVBS [n = 17; 10.5% (P &amp;lt; 0.01)]. A higher proportion of patients with MM on NVBS had a Breslow thickness &amp;gt; 1 mm (n = 23; 38.3%) vs. VBS (n = 30; 29.4%). This study demonstrates a higher number of MM diagnosed incidentally following TBE compared with previous research. Our study focused on a MM-specific cohort who may, potentially, have had lethal skin cancers missed in 28% of cases if TBE was not carried out. Our findings also show that patients are more likely to have noninvasive tumours detected on VBS but more advanced disease on NVBS, further emphasizing the importance of TBE. This study suggests that high-risk patients could benefit from specific surveillance programmes that encourage regular self-skin examination and periodic TBE by a consultant dermatologist to enable early detection and treatment of MM. This study was limited by its retrospective design and a small number of patients from a single institution. We recommend an increased emphasis on patient education on the importance of self-examination which, when complemented by physician-directed TBE, plays a valuable role in the early detection of MM on NVBS. This study provides guidance in designing pathways to target high-risk groups to avoid delays in the diagnosis of MM. Further research to explore trends of MM on NVBS may enable targeted education campaigns in the future.